All abbreviations that have been used in this report are listed here unless the abbreviation is well known (e.g. NHS), or it has been used only once, or it is a non-standard abbreviation used only in figures/tables/appendices, in which case the abbreviation is defined in the figure legend or in the notes at the end of the table.

This section states the key factors that will be addressed by this assessment, and defines the scope of the assessment in terms of these key factors in line with the definitions provided in the NICE scope.

Multiple myeloma (MM) is a type of cancer. The cancer (myeloma) tends to be located at more than one site where there is bone marrow, such as the pelvis, spine and ribs, which is why it is known as MM. MM occurs when a plasma cell begins to proliferate in an unregulated way. Plasma cells are a specialised component of the bone marrow and immune system and they normally produce specific antibodies to fight infection. In MM the myeloma cells produce large quantities of one type of abnormal antibody – monoclonal immunoglobulin protein (M-protein). As the abnormal myeloma cells build in number, the normal functions of bone marrow become impaired to varying degrees of severity because the abnormal myeloma cells may disrupt the function of normal cells, and because the space available for normal bone marrow may be reduced.

Multiple myeloma (MM) is the second most common haematological cancer in the UK, characterised by unregulated plasma cell proliferation. In England and Wales there are approximately 3600 new diagnoses recorded annually, and in 2007 most diagnoses were recorded in people aged 75–79 years. Symptoms and clinical features of MM include fatigue, bone pain and/or fracture, anaemia, the presence of M-protein in serum and/or urine, and hypercalcaemia. The aetiology of MM is unknown and malignant cells display a variety of cytogenetic abnormalities. Myeloma is not curable, but can be treated with a combination of supportive measures and chemotherapy. The aim is to extend the duration and quality of survival by alleviating symptoms and achieving disease control while minimising the adverse effects of the treatment. Survival of patients from diagnosis can vary from months to over a decade. Factors affecting prognosis include burden of disease, type of cytogenetic abnormality present, patient-related factors – such as age and performance status – and treatment response factors.

The a priori methods for systematically reviewing the evidence of clinical effectiveness and cost-effectiveness are described in the research protocol (Appendix 1), which was sent to our expert advisory group for comment. None of the comments we received identified specific problems with the methods of the review. The methods outlined in the protocol are briefly summarised below.

Titles and, where available, abstracts of a total of 1436 records were screened and full copies of 40 references were retrieved. Of these, six were excluded after inspection of the full article (see Appendix 4). Two of these articles were excluded because they were not clinical trial reports, two were abstracts that were excluded because they described maintenance therapy with thalidomide, another abstract was excluded because it did not report on any of the outcomes of interest, and a sixth abstract described a systematic review with meta-analysis. Five full papers described four RCTs that met the inclusion criteria of the review (Figure 1 and Table 4). Each RCT was described by at least one full paper, with linked abstracts also being available. As the full papers provided the most complete data these were the primary source of information for the review.

A systematic literature search was undertaken to identify economic evaluations for first-line treatment with either bortezomib or thalidomide in combination with an alkylating agent and a corticosteroid in people with MM, who are ineligible for HDT with SCT, compared with existing treatments. The details of the search strategy and the methods for the systematic review of cost-effectiveness studies are outlined in Chapter 3 and Appendix 1.